Botanical Products Examined for Prevention of Endometrial Cancer From Tamoxifen Treatment

Division of Cancer Prevention

Tamoxifen, a drug that blocks the effects of the hormone estrogen in breast tissue, is widely used in the treatment of breast cancer in women whose tumors express the cellular receptors for estrogen. Five years of tamoxifen treatment substantially reduces the risk of breast-cancer recurrence, but the drug has several unwanted side effects, including an increased risk of endometrial cancer.

Birgit Dietz, Ph.D., research assistant professor in the Department of Medicinal Chemistry and Pharma­cognosy at the University of Illinois, Chicago (UIC), is searching for natural products that could help prevent endometrial cancer in women taking tamoxifen. Her current work funded by NCI* focuses on two plants – black cohosh (Cimicifuga racemosa) and red clover (Trifolium pratense) – which are available as dietary supplements in the United States. Many women, including breast cancer survivors, use over-the-counter preparations of these herbs for the relief of menopausal symptoms such as hot flashes.

Dr. Dietz and her colleagues first started looking at interactions between black cohosh, red clover, and tamoxifen for safety reasons, since studies had not been done to determine if the herbs interfered with the beneficial effects of tamoxifen in breast tissue. They confirmed that compounds in black cohosh have no estrogen-like activity, making it unlikely that these botanical supplements interfere with the estrogen-blocking effects of tamoxifen.

“Our preliminary data have shown that both black cohosh and red clover contain antioxidative, antiproliferative, anti-inflammatory, and detoxification-enzyme-inducing compounds, which may inhibit carcinogenesis or retard the promotion and progression of precancerous cells,” explained Dr. Dietz.

Their studies have since expanded from safety to chemoprevention of endometrial cancer. In collaboration with the NIH Center for Botanical Dietary Supplements Research, Dr. Dietz’s laboratory has isolated specific compounds from the two herbs with antiproliferative and detoxification-enzyme-inducing properties, and the researchers are currently measur­ing which genes and proteins in cell proliferation pathways are affected by these compounds.

In a study presented** at the 2009 Frontiers in Cancer Prevention Research meeting, held by the American Association for Cancer Research, Dr. Dietz and her colleagues showed that black cohosh reduced tamoxifen-induced endometrial cell proliferation in a dose-dependent manner in human cell lines. Future work will use an animal model of tamoxifen-induced endometrial cancer to quantify the effect of the two botanical compounds.

“Interestingly, another research group recently revealed that black cohosh demonstrated synergistic antiproliferative effects in conjunction with tamoxifen in breast cancer cells, and another research group showed that genistein, a compound in red clover, had a similar effect,” Dr. Dietz reported. “We are also planning to examine the interactions of black cohosh, red clover, and tamoxifen in breast cancer cells and tissue as part of our future work.”

NCI Program Director Maria Agelli, M.D., MS, FACPM, commented, “With a well designed study, moving progressively from cell line to animal model experiments, Dr. Dietz’s research will provide experimental evidence critical to assess the ability, and possible role, of black cohosh and red clover in the prevention of endometrial cancer secondary to treatment with tamoxifen.”